We shall investigate the effects of cannabinoids, delta 9-tetrahydrocannabinol, cannabidiol and cannabichromene as well as crude marihuana extract on (1) the male sex hormone and (2) corticosteroid hormone systems in the male rat. In (1), acute, subchronic and chronic studies will be carried out in the hypothalamopituitary-male gonadal system in intact, hypophysectomized and/or castrate animals. Serum gonadotropin and androgen levels will help to indicate sites of stimulatory or inhibitory effects or effects on steroid transport and/or feedback regulation. Any secondary sex organ weight changes should also assist in these determinations. Androgen receptor activity studies in testis and ventral prostate may indicate androgen or anti-androgen action by cannabinoids. Also, measuring androgen binding protein content of the testes will contribute to these investigations on cannabinoid effects. In (2) we shall investigate cannabinoid effects on the hypothalamo-pituitary-adrenal system in intact, hypophysectomized or adrenalectomized animals. Serum corticosterone and ACTH levels coupled with adrenal weight charges will assist in determining site(s) of stimulatory, inhibitory or feedback effects. Direct effects on thymus or liver will be investigated by measuring glucocorticoid cytoplasmic receptor activity as well as by possible tissue weight changes. Thus, in the proposed studies, we shall seek the site(s) and mode(s) of action of cannabinoids on the androgenic and corticosteroid hormone systems.